Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function

Congshan Sun, Vanessa De Mello, Abdalla Mohamed, Huascar P. Ortuste Quiroga, Amaya Garcia-Munoz, Abdullah Al Bloshi, Annie M. Tremblay, Alexander von Kriegsheim, Elaina Collie-Duguid, Neil Vargesson, David Matallanas, Henning Wackerhage, Peter S. Zammit* (Corresponding Author)

*Corresponding author for this work

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Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. siRNA knockdown or retroviral-mediated expression of wildtype human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene Wwtr1-/-) knockout mice, there were no overt effects on regeneration. Conversely, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+: Yapfl°x/fl°x: Rosa26Lacz mice produced a marked regeneration deficit. To identify potential mechanisms, microarray analysis showed many common TAZ/YAP target genes, but TAZ also regulates some genes independently of YAP, including myogenic genes such as Pax7, Myf5 and Myod1 (ArrayExpress - E-MTAB-5395). Proteomic analysis revealed many novel binding partners of TAZ/YAP in myogenic cells, but TAZ also interacts with proteins distinct from YAP that are often involved in myogenesis and aspects of cytoskeleton organization (ProteomeXchange - PXD005751). Neither TAZ nor YAP bind members of the Wnt destruction complex but both regulated expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to enhance myogenic differentiation.
Original languageEnglish
Pages (from-to)1958-1972
Number of pages15
JournalStem Cells
Issue number8
Early online date27 Jun 2017
Publication statusPublished - 1 Aug 2017

Bibliographical note

Funded by MRC grant G11001931 to HW and PSZ, European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement number 262948–2 (BIODESIGN), with additional support from AssociationFrançaise Contre les Myopathies, BBSRC, Sarcoma UK and Friends of Anchor.


  • Taz
  • satellite cells
  • muscle stem cells
  • Tead
  • Yap


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